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Aviceda Therapeutics Announces Phase 2b SIGLEC Results for AVD-104 in Geographic Atrophy

via Business Wire

SIGLEC Phase 2b data support AVD-104 as a potential therapy to reduce GA lesion growth, preserve and improve visual acuity, and reduce conversion to neovascular AMD across all GA lesion types at 1 year

Both AVD-104 dosing arms showed 31-38% less growth than prior randomized, placebo-controlled trials or previously reported natural history cohorts; Primary endpoint analysis comparing the rate of change in GA area between AVD-104 and monthly avacincaptad pegol showed no statistical difference

Participants in the monthly AVD-104 treatment arm experienced an improved mean visual acuity (+0.6-letters) over the entire study period, and 28.9%, 16.9% and 4.8% of participants achieved gains of ≥ 5, ≥ 10, and ≥ 15-letters, respectively

Conversion to neovascular AMD occurred in only 2% of participants in the monthly treatment arm

Aviceda Therapeutics (“the Company” or “Aviceda”), a clinical-stage biotechnology company developing innovative therapies for retinal diseases, today announced topline results from its SIGLEC Phase 2b study evaluating AVD-104 in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

The primary endpoint analysis showed no statistical difference in the rate of change in GA area between AVD-104 versus monthly avacincaptad pegol. Imbalances in key baseline lesion characteristics across treatment arms contributed to the lesion-growth outcomes. In addition, the study demonstrated that treatment with AVD-104 resulted in clinically meaningful reductions in GA lesion-growth rates versus natural history, sustained visual acuity gains, and a favorable safety profile with a low rate of neovascular AMD conversion.

Key Findings from the Monthly AVD-104 Treatment Arm at 12 Months

  • GA Lesion growth rate illustrates approximately 31% reduction versus growth rates from Sham1 and natural history2 rates.
  • Sustained improvement in mean best-corrected visual acuity (BCVA) over the entire study period (+0.6-letters at Month 12), which has not been observed in other GA clinical trials to date.
  • Categorical BCVA gains of ≥ 5, ≥ 10, and ≥ 15-letters were achieved in 28.9%, 16.9% and 4.8% of participants, respectively.
  • Low CNV conversion rate, with 2% of participants developing neovascular AMD.
  • No drug-related serious adverse events were observed in participants treated with AVD-104. The most common treatment-emergent adverse event (TEAE) in participants was floaters.

“The SIGLEC study represents the first clinical validation of glycoimmune checkpoint therapy to modulate macrophages and microglia to treat geographic atrophy,” said Jeffrey Nau, PhD, MMS, Chief Executive Officer of Aviceda Therapeutics. “These results reinforce our belief that AVD-104 can provide meaningful functional vision benefit while reducing lesion progression, and has the potential to become a differentiated therapy addressing a significant unmet medical need for patients living with GA.”

“We are encouraged by the magnitude of visual acuity gains, including protection from significant vision loss, reduction in lesion growth relative to historical sham and expected natural history, and the compelling safety profile observed with monthly AVD-104, in this first-ever multi-dose trial of AVD-104,” said David Callanan, MD, Chief Medical Officer of Aviceda Therapeutics. “AVD-104 demonstrated a favorable safety and tolerability profile, with a low rate of neovascular AMD conversion and no serious drug-related adverse events, including no retinal vasculitis. We believe AVD-104 is poised to address critical gaps in current GA therapies that limit adoption, such as the lack of functional vision benefit and the safety limitations of neovascular AMD conversion.”

The Company expects to present AVD-104 data from the Phase 2b SIGLEC trial at medical congresses in 2026.

Aviceda plans to advance AVD-104 into two randomized, sham-controlled Phase 3 confirmatory studies. Final design of the clinical development program, informed by greater understanding of OCT-based baseline lesion characteristics and global regulatory interactions are underway, with trial initiation expected in 2026.

About AVD-104

AVD-104 is a poly sialic acid coated nanoparticle. The poly-sialic acid ligands present on the surface of the nanoparticle interact with sialic acid-binding immunoglobulin-like lectins (SIGLEC) receptors -7, -9, and -11 found on macrophages, microglia, and monocytes in the retina. Macrophages, microglia, and circulating monocytes have been shown to be present in areas of retinal atrophy in patients with geographic atrophy secondary to age-related macular degeneration. The binding of AVD-104 to SIGLEC receptors 7, 9, and 11 inhibits pro-inflammatory cytokine release, phagocytosis, and reduces monocyte differentiation into M1 macrophages.

SIGLEC Trial Design

SIGLEC is a randomized, multi-center, double-masked, active comparator-controlled Phase 2b clinical trial comparing the safety and efficacy of AVD-104 to avacincaptad pegol in patients with GA secondary to age-related macular degeneration (AMD). The study enrolled a total of 300 patients. Patients had an average age of 79 years with an average baseline visual acuity of 58.5 letters. All participants were enrolled at investigational centers in the United States.

Patients were randomized to receive an intravitreal dose of 2 mg AVD-104 every other month (n=100), 1 mg AVD-104 monthly (n=100), or 2 mg avacincaptad pegol (n=100) for a treatment period of 24 months, with an interim analysis at 12 months. The primary outcome measure of the study was the rate of change in GA lesion growth (slope) from baseline as measured by fundus autofluorescence (FAF) through 12 months for the study eye. The study included multiple pre-specified visual function measures to assess the effects of AVD-104 on vision: change from baseline in ETDRS BCVA, change from baseline in contrast sensitivity, and change from baseline in low-luminance best corrected visual acuity (LLVA).

About Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD)

Age-related macular degeneration (AMD) is the major cause of moderate and severe loss of central vision in aging adults, affecting both eyes in the majority of patients. The macula is a small area in the central portion of the retina responsible for central vision. As AMD progresses, the loss of retinal photoreceptors and the underlying blood vessels in the macula results in marked thinning and/or atrophy of retinal tissue. Geographic atrophy, the advanced stage of AMD, leads to further irreversible loss of vision in these patients. Currently, there are two anti-complement therapies approved by the U.S. Food and Drug Administration (FDA) and no therapies approved by the European Medicines Agency (EMA) for patients with geographic atrophy.

About Aviceda Therapeutics

Aviceda Therapeutics is a private, clinical-stage biotechnology company and the world leader in glyco-immune checkpoint therapeutics. Aviceda is developing AVD-104, an intravitreal sialic acid coated nanoparticle intended for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). This nanoparticle technology harnesses the body’s natural ‘self-recognition’ system to control aberrant inflammation. By targeting the interaction between sialic acids on cell surfaces and Siglec immune receptors, we aim to modulate immune responses and open new possibilities for treating chronic disease.

Along with AVD-104, Aviceda has a broad pipeline of products in development in ophthalmology and multiple other therapeutic areas, including immunology, fibrosis, oncology, and neurology.

Visit the company website to learn more about Aviceda Therapeutics and follow the company on LinkedIn and X (formerly Twitter).

References

  1. Khanani, A. M., Patel, S. S., Staurenghi, G., Tadayoni, R., Danzig, C. J., Eichenbaum, D. A., ... & Danzig, C. (2023). Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial. The Lancet, 402(10411), 1449-1458.
  2. Sunness, J. S., Margalit, E., Srikumaran, D., Applegate, C. A., Tian, Y., Perry, D., ... & Bressler, N. M. (2007). The long-term natural history of geographic atrophy from age-related macular degeneration: enlargement of atrophy and implications for interventional clinical trials. Ophthalmology, 114(2), 271-277.

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